Molecular and genomic epidemiology approaches have the potential?as yet largely unrealized?to add powerful tools to the malaria elimination toolkit. We are already using highly sensitive molecular testing for national malaria surveillance and to guide mass drug administration in Myanmar. Our haplotype analyses of the emergence and dissemination of drug resistance helped prompt the World Health Organization to launch a regional campaign to eliminate falciparum malaria from Southeast Asia. High throughput protein and peptide microarrays that measure variant-specific antibody responses may prove valuable for estimating exposure to specific parasite and mosquito species. Genome sequencing and genotyping large numbers of clinical samples yields information that can be used to understand parasite migration patterns. The Molecular and Genomics Core will help Project 1 and 2 investigators develop and deploy high-sensitivity and high-throughput molecular, genomics and serological techniques and tools to support these goals, with a focus on facilitating the transition of most of these capabilities to regional laboratories over the course of the study. In Aim 1 we propose to establish, or strengthen capacity for, high-throughput ultrasensitive PCR at regional ICEMR laboratories in Myanmar, China and Bangladesh and incorporate new diversity-reflecting microarray-based sero-surveillance tools to measure malaria and mosquito exposure. In Aim 2, we will develop and implement approaches to increase parasite DNA representation in field samples prior to sequencing. These DNA samples will be used to generate high-throughput sequence data for Plasmodium falciparum and Plasmodium vivax in Aim 3, and to design next-generation DNA protein and peptide microarrays. The data generated will be analyzed by all three Projects, to generate accurate estimates of the true malaria burden in the region, to characterize the emergence and spread of drug resistance, and to integrate all these variables into a regional model of malaria epidemiology and transmission, upon which public health interventions can be based. Finally, Aim 4 seeks to disseminate the generated data to the wider scientific community, though the use of public data repositories and a project-specific web portal, to help guide national and regional malaria control and elimination policies. .